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Role of Pattern-Recognition Receptors (PRR) in the activation of rheumatoid arthritis synovial fibroblasts

Role of Pattern-Recognition Receptors (PRR) in the activation of rheumatoid arthritis synovial fibroblasts.

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Role of Pattern-Recognition Receptors (PRR) in the activation of rheumatoid arthritis synovial fibroblasts

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  1. Role of Pattern-Recognition Receptors (PRR) in the activation of rheumatoid arthritis synovial fibroblasts The recognition of pathogen-associated molecular pattern molecules (PAMPs) or damage-associated molecular pattern molecules (DAMPs) by pattern-recognition receptors (PRR) may play an important role in the pathogenesis of autoimmune arthritis. PRRs are expressed on cells of the innate immune system representing a first line of defense against infections and cellular damage. Activation of synovial fibroblasts via PRRs such as Toll-like receptors (TLR) and the NOD-like receptors NOD1 and NOD2 results in the production of proinflammatory cytokines and destructive enzymes. The goal of the project is to evaluate the effect of various PRR ligands on synovial fibroblasts and to assess the importance of these molecular pathways for the pathogenesis of rheumatoid arthritis. The role of endogenous DAMPs such as necrotic cells and nucleic acids in the activation of synovial fibroblasts has been assessed, as well as the interplay of the different PRRs in proinflammatory signaling pathways in rheumatoid arthritis synovial fibroblasts.

  2. Contribution of PRRs in the pathogenesis of RA: A model exogenous/ endogenous ligands TLR4 TLR1 or TLR6 TLR2 TLR5 TLR3 NOD1 Endosome NOD2 Cytokines, Chemokines, Matrix Metalloproteinases Feedback loop Joint inflammation and destruction

  3. Publications: • Expression, regulation, and signaling of the pattern-recognition receptor nucleotide-binding oligomerization domain 2 in rheumatoid arthritis synovial fibroblasts. Ospelt C, Brentano F, Jüngel A, Rengel Y, Kolling C, Michel BA, Gay RE, Gay S. • Overexpression of toll-like receptors 3 and 4 in synovial tissue from patients with early rheumatoid arthritis: toll-like receptor expression in early and longstanding arthritis. Ospelt C, Brentano F, Rengel Y, Stanczyk J, Kolling C, Tak PP, Gay RE, Gay S, Kyburz D. Arthritis Rheum. 2008 Dec;58(12):3684-92. • RNA released from necrotic synovial fluid cells activates rheumatoid arthritis synovial fibroblasts via Toll-like receptor 3. Brentano F, Schorr O, Gay RE, Gay S, Kyburz D. • Arthritis Rheum. 2005 Sep;52(9):2656-65. • Chemokine secretion of rheumatoid arthritis synovial fibroblasts stimulated by Toll-like receptor 2 ligands. Pierer M, Rethage J, Seibl R, Lauener R, Brentano F, Wagner U, Hantzschel H, Michel BA, Gay RE, Gay S, Kyburz D. J Immunol. 2004 Jan 15;172(2):1256-65. • Bacterial peptidoglycans but not CpG oligodeoxynucleotides activate synovial fibroblasts by toll-like receptor signaling. Kyburz D, Rethage J, Seibl R, Lauener R, Gay RE, Carson DA, Gay S. Arthritis Rheum. 2003 Mar;48(3):642-50.

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